It has been suggested that hypothyroidism predisposes to the development of human breast cancer. However, studies concerning the effects of hypothyroidism on mammary cancer induced in rats by dimethylbenzanthracene (DMBA) have yielded inconsistent results. Our overall objectives in the proposed study are: A) To examine selectively the effects of hypothyroidism and of iodine deficiency on the induction and growth phases of DMBA-induced mammary carcinoma in the rat; B) To study the mechanism of these effects; and C) To examine the regulation of iodine metabolism and of conversion of thyroxine to triiodothyronine within the tumor, in relation to tumor growth. We plan to examine the effects of iodine deficiency with and without thyroxine replacement, on DMBA-induced carcinogenesis. We will also study the effects of mild hypothyroidism induced by low doses of propylthiouracil, to avoid the decrease in food intake characteristic of severe hypothyroidism. Further, we will compare the effect of hypothyroidism induced prior to the administration of DMBA with that produced after DMBA administration. The effects of hypothyroidism on the prolactin receptors and on the estrogen dependence of the tumors will also be examined. Mammary tissue concentrates and organifies iodine, raising the possibility that iodine plays a role in its metabolism. We plan to study the uptake of 131I by DMBA-induced tumors, and examine the response of this process to oophorectomy, and its relation to tumor growth. We will also determine whether the DMBA tumor is one of the several tissues that can convert thyroxine to triiodothyronine (73), and investigate the effect of oophorectomy on this process. The production of T3 within the tumor is of interest, because this hormone through its demonstrated capacity to bind to receptors associated with nuclear DNA, could affect the rate of tumor growth.